An experimental myocardial infarction (MI) model in cats, which maintains a propensity to both chronic ventricular ectopic activity (VEA), and long-term cellular electrophysiologic abnormalities (for at least 6 months after acute coronary ligation), has recently been developed in this laboratory. The present proposal is designed to study mechanisms of the chronic VEA, and the characteristics of the long-term cellular electrophysiologic abnormalities, in this new model. In the preliminary studies, a propensity to spontaneous ventricular arrhythmias occurred in 50% of the cats surviving the acute infarction, and abnormal transmembrane action potentials were recorded from endocardial cells overlying the infarction zone in 90% (29 of 32) of the cats studied 1 week to 6 months after infarction. In the proposed protocol, the mechanisms of arrhythmias will be studied by surface electrogram and microelectrode mapping of the infarct zone and surrounding normal tissue during initiation of and/or the persistence of ventricular arrhythmias, in order to elucidate the role of automatic activity and/or re-entry in the chronic VEA. Abnormal cell membrane ionic activity will be studied by characterizing the effect of exposure of 1-verapamil and/or tetradotoxin to selectively block "slow-channel" and/or "fast-channel" activity. Furthermore, the effect of superfusion of the isolated preparation with antiarrhythmic drugs will be studied in (1) cells having long-term electrophysiologic abnormalities after surviving the acute MI, (2) cells which appear normal during regular stimulation but which have abnormal transmembrane action potentials during the stress of premature stimulation of rapid pacing, and (3) in normal cells from non-infarcted areas of the same heart. An attempt will be made to correlate the effects of the antiarrhythmic agents on arrhythmias recorded during study of the intact animal prior to sacrifice, with the effect of these same agents at a cellular level during isolated tissue studies. The overall goals include a better understanding of mechanism(s) of chronic VEA after healing of MI, and of the electrophysiologic basis for these arrhythmias.